Drug-loaded nanoparticles induce immunogenic cell death and efficiently target cells from glioblastoma patients.

in Nanomedicine (London, England) by Ada Tushe, Elena Marinelli, Beatrice Musca, Annavera Ventura, Sara Zumerle, Olga Slukinova, Giulia Zampardi, Francesco Volpin, Camilla Bonaudo, Alessandro Della Puppa, Mathieu Repellin, Giulia Guerriero, Giovanna Lollo, Susanna Mandruzzato

TLDR

  • Diaminocyclohexane-platinum II (DACHPt)-loaded polymeric nanosystems demonstrated enhanced cytotoxicity and immunogenic cell death induction in glioblastoma multiforme cells, presenting a promising therapeutic strategy.

Abstract

Glioblastoma multiforme (GBM) is characterized by a highly immunosuppressive tumor microenvironment (TME), posing significant challenges for efficient therapy's outcomes. Nanomedicine combined with immunotherapy holds the potential to modulate the TME and reactivate immune responses. This study proposes a polymeric nanosystem (NPs) encapsulating diaminocyclohexane-platinum II (DACHPt), an oxaliplatin derivative, to induce immunogenic cell death (ICD) in GBM cells. An ionic-gelation technique was employed to generate polymeric nanoparticles (NPs) with an approximate size of 200 nm. NPs internalization was analyzed in GBM cell lines,-derived macrophages, and in leukocytes and tumor cells from GBM patient via flow cytometry and confocal imaging. ICD was assessed by measuring two of its main markers: adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1). NPs were efficiently incorporated by myeloid and tumor cells, but not by lymphocytes. DACHPt-loaded NPs demonstrated enhanced cytotoxicity compared to free drug, with increased ATP and HMGB1 release from GBM cells, confirming ICD induction. Our findings suggest that DACHPt-loaded NPs represent a promising therapeutic strategy capable of targeting both tumor cells and tumor-promoting immune cells while inducing ICD.

Overview

  • The study aims to investigate a polymeric nanosystem (NPs) encapsulating diaminocyclohexane-platinum II (DACHPt) to induce immunogenic cell death (ICD) in glioblastoma multiforme (GBM) cells.
  • The NPs were generated using an ionic-gelation technique and had an approximate size of 200 nm.
  • The primary objective is to evaluate the potential of DACHPt-loaded NPs as a therapeutic strategy for targeting both tumor cells and tumor-promoting immune cells while inducing ICD.

Comparative Analysis & Findings

  • The study demonstrated that DACHPt-loaded NPs were efficiently incorporated by myeloid and tumor cells, but not by lymphocytes.
  • The results showed that DACHPt-loaded NPs demonstrated enhanced cytotoxicity compared to free drug, with increased ATP and HMGB1 release from GBM cells, confirming ICD induction.
  • The findings suggest that DACHPt-loaded NPs represent a promising therapeutic strategy for GBM treatment, targeting both tumor cells and tumor-promoting immune cells while inducing ICD.

Implications and Future Directions

  • The study's findings have implications for the development of novel therapeutic strategies for GBM treatment, particularly those that utilize nanomedicine and immunotherapy.
  • Future studies should investigate the optimal dosage and administration schedule of DACHPt-loaded NPs, as well as their potential combination with other therapies.
  • The study's results also highlight the need for further research on the molecular mechanisms underlying immunogenic cell death and its relationship with the tumor microenvironment.
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